1. Field of the Invention
The present invention relates to a method and apparatus for non-invasively measuring glucose concentration in a living body without blood sampling.
2. Background Art
Hilson et al. report facial and sublingual temperature changes in diabetics following intravenous glucose injection (non-patent document 1). Scott et al. discuss the issue of diabetes mellitus and thermoregulation (non-patent document 2). Based on such researches, Cho et al. suggest a method and apparatus for determining blood glucose concentration by temperature measurement without requiring the collection of a blood sample (patent document 1 and 2).
Various other attempts have been made to determine glucose concentration without blood sampling. For example, a method has been suggested (patent document 3) whereby a measurement site is irradiated with near-infrared light of three wavelengths, and the intensity of transmitted light as well as the temperature of the living body is detected. Representative values of the second-order differentiated values of absorbance are then calculated, and the representative values are corrected in accordance with the difference of the living body temperature from a predetermined reference temperature. The blood sugar level corresponding to the thus corrected representative values is then determined. An apparatus is also provided (patent document 4) whereby a measurement site is heated or cooled while monitoring the living body temperature. The degree of attenuation of light based on light irradiation is measured at the moment of temperature change so that the glucose concentration responsible for the temperature-dependency of the degree of light attenuation can be measured. Further, an apparatus is reported (patent document 5) whereby an output ratio between reference light and the light transmitted by an irradiated sample is taken, and then the glucose concentration is calculated by a linear expression of the logarithm of the output ratio and the living body temperature.
Another method for determining the glucose concentration accurately by incorporating corrections is proposed (Patent Document 6). In this method, detection results concerning a plurality of different phenomena, such as infrared absorbance, scattering, and polarimetry, are utilized to determine glucose concentration. In another method, measurements are made in an optical measurement system while removing the influences of component substances other than glucose and making corrections (Patent Document 7). Removal of the influences of irrelevant component substances has been applied to the measurement of not only glucose but also to various other substances. For example, a method has been proposed (Patent Document 8) for removing the influence of irrelevant component substances when measuring the oxygen consumption amounts or oxygen contents in human bodies.
(Non-Patent document 1)
R. M. Hilson and T. D. R. Hockaday, “Facial and sublingual temperature changes following intravenous glucose injection in diabetics,” Diabete & Metabolisme, 8, pp. 15-19: 1982
(Non-Patent Document 2)
A. R. Scott, T. Bennett, I. A. MacDonald, “Diabetes mellitus and thermoregulation,” Can. J. Physiol. Pharmacol., 65, pp. 1365-1376: 1987
(Patent Document 1)
U.S. Pat. No. 5,924,996
(Patent Document 2)
U.S. Pat. No. 5,795,305
(Patent Document 3)
JP Patent Publication (Kokai) No. 2000-258343 A
(Patent Document 4)
JP Patent Publication (Kokai) No. 10-33512 A (1998)
(Patent Document 5)
JP Patent Publication (Kokai) No. 10-108857 A (1998)
(Patent Document 6)
JP Patent Publication (Kohyo) No. 2001-524342 A
(Patent Document 7)
JP Patent Publication (Kokai) No. 10-325794 A (1998)
(Patent Document 8)
JP Patent Publication (Kohyo) No. 2003-517342 A
Glucose (blood sugar) in the blood is used for glucose oxidation reaction in cells to produce necessary energy for the maintenance of living bodies. In the basal metabolism state, in particular, most of the produced energy is converted into heat energy for the maintenance of body temperature. Thus, it can be expected that there is some relationship between blood glucose concentration and body temperature. However, as is evident from the way sicknesses cause fever, the body temperature also varies due to factors other than blood glucose concentration. While methods have been proposed to determine blood glucose concentration by temperature measurement without blood sampling, they lack sufficient accuracy.
Methods of determining glucose concentrations based on the intensity of transmitted light, such as near-infrared, have also been devised. However, it is difficult to perform accurate analysis using these methods because the identities of the absorbance peaks of near-infrared light are unclear. In order to solve this problem, correction techniques have been proposed that aim to remove interfering substances in an optical measurement system, but none of them are accurate enough to be practical.